Changes in Treatment Patterns over Time Among Real-World Patients with Follicular Lymphoma at Predominantly Community Facilities in the US

BACKGROUND: Follicular lymphoma (FL) is characterized by a relapsing and remitting course that can lead to multiple lines of therapy (LOTs). While frontline treatments are well-established, optimal treatment in third line (3L) or later is not well-defined and the introduction of novel therapies in recent years has increased treatment options. This study examines changes in treatment patterns over the time periods of 2015–2018 and 2019–2023 for first (1L) through fifth line (5L) among US real-world FL patients (pts).

METHODS: This retrospective, observational study used Optum Market Clarity claims and electronic health record (EHR) FL data, which has 93% encounters from confirmed community facilities in the US. Inclusion criteria were: ≥1 inpatient or ≥2 outpatient claims or ≥1 EHR record with diagnosis of FL from 2008–2023 (index date); ≥12 months pre-index enrollment or EHR clinical activity with no evidence of cancer; ≥1 LOT initiated in 2015 or later.

LOTs consist of all therapies administered in the first 28 days of treatment. Adding new therapies after this period initiated a new LOT. Maintenance lines were excluded from analysis. This study is descriptive only and no statistical testing was performed.

RESULTS: In 1L, there were 2906 pts from 2015–2018 and 1878 from 2019–2023. Most treatments were rituximab (R)-based and changed little over time. For 2015–2018 vs 2019–2023, >80% of treatments were either R + chemo (consisting of R + bendamustine, R-CHOP, R-EPOCH, R-ICE, and similar therapies) (61% vs 58%) or R monotherapy (mono) (28% vs 25%). Chemo (mono or combination treatment with platinum-based therapies, cytarabine, vincristine, and similar), the third largest category, was unchanged (5% vs 5%). Small increases were seen in ofatumumab (OF) or obinutuzumab (OB) + bendamustine (2% vs 5%) and R + lenalidomide (R2) (1% vs 2%). Utilization of other therapies was uncommon.

In 2L there were 1300 pts from 2015–2018 and 956 from 2019–2023. R-based regimens were the most common, but were less utilized and had larger decreases between time periods than in 1L. For 2015–2018 vs 2019–2023, decreases were seen in R mono (41% vs 34%) and R + chemo (35% vs 31%). Increases were seen in R2 (2% vs 6%), OF and OB mono or with bendamustine (3% vs 7%), and lenalidomide or venetoclax mono (2% vs 5%).

In 3L, there were 614 pts from 2015–2018 and 497 from 2019–2023. R mono was the most common therapy but dropped between periods (41% vs 28%). R + chemo decreased slightly (23% vs 21%) as did PI3Ki-containing (5% vs 2%). Similar over time were chemo (10% vs 10%) and BTKi-containing (7% vs 8%). Increases were seen in OF and OB monotherapy (1% vs 4%), R2 (5% vs 7%), lenalidomide or venetoclax mono (3% vs 9%), CAR-T (0% vs 2%), and tazemetostat (taz)-containing (0% vs 2%).

In 4L, there were 344 pts from 2015–2018 and 288 from 2019–2023. As in 3L, R mono was the most common therapy but dropped between periods (46% vs 28%), while R + chemo showed a small decrease (20% vs 17%). Similar over time were PI3Ki-containing (5% vs 5%), and R2 (3% vs 4%). Chemo (11% vs 13%) increased slightly, and increases were also seen in BTKi-containing regimens (7% vs 11%), OF or OB mono (0% vs 4%), lenalidomide or venetoclax mono (3% vs 8%), CAR-T (0% vs 2%), and taz-containing (0% vs 2%).

In 5L, there were 180 pts from 2015–2018 and 149 from 2019–2023. R mono was the most common therapy, with utilization dropping between periods (56% vs 32%). Similar across time were R + chemo (12% vs 13%), BTKi-containing (9% vs 10%), and PI3Ki-containing (4% vs 3%). Increases were seen in lenalidomide or venetoclax mono (4% vs 13%), chemo (6% vs 9%), R2 (3% vs 7%), CAR-T (0% vs 3%), and taz-containing (0% vs 3%).

While mosunetuzumab, a bispecific monoclonal antibody (bsAb), was approved in late 2022, there were not sufficient pts to assess utilization.

CONCLUSIONS: R-based regimens, particularly R mono, continue to be the mainstay of FL treatment in US community facilities. While 1L treatments changed little over time, in later lines, R mono use decreased, replaced by more novel therapies such as R2, BTKis, OF, OB, lenalidomide, venetoclax, taz, and CAR-T. Utilization of newer therapies in later lines in the community remains low, with the standard treatments of R mono and R + chemo making up 44% to 65% of treatments in 2L–5L during 2019–2023. Future research should evaluate use of other novel therapies such as bsAbs and the impact of later line sequencing on clinical outcomes.